I'm studying (on a language holiday) in Guanajuato right now and it feels quite safe. It is an interesting city, with lots of cultural activities, and a lively scene in the evenings in the city (although there are a LOT of teenagers and young adults hanging out - it's a university town). People are very friendly. I walk down to the city center in the evening on my own but take a taxi back.
My dad and stepmother go to Puerto Vallarta every winter and feel quite comfortable there. They've also toured around a bit in a rental car or on buses and never had problems.
I go to Mexico City on business every few months. There, I don't feel so secure. I probably am too cautious, but I don't go out much on my own - only with my colleagues. I do feel comfortable walking around a bit near the hotel where I stay and near our office, but that's about it. Almost every colleague I've spoken to has a robbery/mugging story to tell - not that much different from New York City in the 80s, really.